Exploiting biocatalysis in performing organic reactions

کد مقاله : 1347-ICOC

نویسندگان

حمیدرضا کلهر * دانشگاه صنعتی شریف

چکیده مقاله

Biocatalysis has emerged as a crucial aspect of modern organic synthesis. Nature has optimally used enzymes to perform highly selective reactions with an unmatched rate in biosynthesis and metabolic repertoires of the cells. In recent years, turning enzymes into biocatalysts to carry out non-native reactions has attracted enormous interests. In our recent studies, we have been able to use lysozyme, a hydrolase, for the synthesis of β-amino carbonyl compounds through a directed three-component Mannich reaction in aqueous. Additionally, lysozyme was encapsulated using metal organic frame work (MOF), resulting in the enhanced activity for the Mannich reaction. In another approach, lysozyme and its immobilized form on g-C3N4 surface was exploited to synthesize 4-substitited-1H-1,2,3 triazole. The immobilized enzyme showed enhanced activity and reusability over seven cycles. To show the synthetic utility of triazoles, disubstituted -1,2,3-triazoles from α,β-unsaturated carbonyl compounds were synthesized in a cascade chemo-enzymatic synthesis. Using recombinant falvin reductase, tetraketone synthesis was afforded. The mechanism of the synthesis turned out to be by Knoevenagel condensation-Michael addition. Using computational studies Ser49 was identified as a key residue, stabilizing the enolate intermediate and faciliting hydrogen bond formation during the enolization of dimedone, thereby initiating both steps in the tetraketone synthesis cascade. Using site-directed mutagenesis, mutation of Ser49 to Ala (Ser49Ala) demonstrated that the activity was greatly abolished.

کلیدواژه ها

Biocatlaysis, Immobilized enzyme, disubstituted -1,2,3-triazoles, Flavin reductase, lysozyme

وضعیت: پذیرفته شده